Findings on the efficacy of adjuvant chemotherapy (ACT) of locally advanced cervical cancer (LACC) after the concurrent chemoradiation (CCRT) therapy were inconsistent, and the OUTBACK trial was expected to shed some light regarding the topic. Its results on ACT in LACC were negative, with the conclusion of not to use it. The objective of this review was to present the inconsistencies of previous studies, along with the OUTBACK trial in more detail, and to rethink whether its results provide an unambiguous and definite answer to the optimal position of ACT in the treatment of LACC. To critically appraise the OUTBACK trial and understand the consequences of its results, we used only randomized controlled studies (RCTs) on ACT in LACC that have been included in high-quality systematic reviews and meta-analyses. We calculated the pooled prediction intervals using a random effects meta-analysis of all published randomized studies including the OUTBACK trial. After combining the OUTBACK trial with the results of four previous randomized trials, the pooled hazard ratio for overall survival benefit of CCRT + ACT was 0.95 (95% CI 0.75; 1.20). The pooled hazard ratio of the four previous trials was 1.00 (95% CI 0.69; 1.44). The OUTBACK trial improved the precision of the pooled estimate, but the clinical heterogeneity and the consequent prediction intervals are still very wide, and with 95% reliability, we can expect that if the new study, using a similar approach to the ACT, on a randomly selected patient population from the presented five trials is conducted, its hazard ratio for overall survival after ACT would be between 0.47 and 1.93. In conclusion, there is an absolute need for further research in order to optimally define the position of ACT in the treatment of LACC.

Background/Objectives: Clear cell renal cell carcinoma (ccRCC) is characterized by dysregulated apoptotic and inflammatory signaling, yet the tissue-level behavior of several candidate regulators remains poorly defined. Materials and Methods: We quantified ectodysplasin A2 receptor (EDA2R), TNF-receptor-associated factor 7 (TRAF7) and the apoptotic fragments cleaved-PARP1 and cleaved-CASP3 by immunofluorescence in 49 ccRCC and 27 matched non-tumoral cortex samples and analyzed the corresponding transcripts in TCGA-KIRC and GTEx. Results: TRAF7 protein was higher in tumor than in control tissue (median 0.81% vs. 0.63% positive area, p = 0.015), an increase concentrated in grade 2–3 tumors, whereas EDA2R and the apoptotic fragments did not differ (all p > 0.59). The positive EDA2R–cleaved-PARP1 correlation in low-grade tumors (ρ = +0.54, p = 0.002) was attenuated in high-grade tumors (ρ = +0.06, p = 0.84). In TCGA-KIRC, EDA2R mRNA was overexpressed in tumors, and higher expression was associated with better overall survival (HR = 0.60, p = 0.0011), including after mutual adjustment for the four transcripts (HR = 0.66, p = 5.3 × 10⁻⁵) and after adjustment for age, sex, stage and grade (HR per standard deviation = 0.83, p = 0.008). TRAF7 mRNA did not differ between tumor and normal tissue, but higher levels were associated with worse overall survival after the same adjustment (HR = 1.38, p < 0.001). Conclusions: TRAF7 and EDA2R show opposite, marker-specific discordance between protein- and transcript-level data across cohorts, consistent with, but not demonstrating, regulation beyond transcription. EDA2R is a candidate transcript-level prognostic marker requiring validation, and TRAF7 is a protein-level feature of ccRCC; paired RNA–protein and functional studies are needed.